Oxidation of the skeletal muscle Ca2+ release channel alters calmodulin binding

1 Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030; and 2 Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan 48824-1224 This study presents evidence for a close relationship between the oxidation state of the skeletal muscle Ca 2+ release channel (RyR1) and its ability to bind calmodulin (CaM). CaM enhances the activity of RyR1 in low Ca 2+ and inhibits its activity in high Ca 2+ . Oxidation, which activates the channel, blocks the binding of 125 I-labeled CaM at both micromolar and nanomolar Ca 2+ concentrations. Conversely, bound CaM slows oxidation-induced cross-linking between subunits of the RyR1 tetramer. Alkylation of hyperreactive sulfhydryls (